Rivaroxaban vs Apixaban

## Overview

Rivaroxaban and apixaban are both direct oral factor Xa inhibitors (DOACs) used for stroke prevention in non-valvular atrial fibrillation (AF), VTE treatment, and VTE prophylaxis. The key pharmacokinetic difference is renal clearance: apixaban has lower renal clearance, making it more appropriate in moderate CKD.

## Mechanism of Action

Both bind directly to the active site of factor Xa, inhibiting conversion of prothrombin to thrombin. Unlike warfarin, they target a single coagulation factor and do not require monitoring (stable predictable pharmacokinetics).

## Pharmacokinetics

Rivaroxaban: once daily with evening meal for AF indication (food increases absorption from ~66% to ~80%+), half-life 5–9 h (healthy) to 11–13 h (elderly), ~33% renal clearance. Apixaban: twice daily (10 mg BID for 7 days, then 5 mg BID for VTE; 5 mg BID for AF), half-life 8–15 h, ~27% renal clearance, food independent.

## Bleeding Profile

Pivotal trials: ROCKET-AF (rivaroxaban) vs ARISTOTLE (apixaban) for AF. ARISTOTLE demonstrated apixaban superior to warfarin in both stroke prevention and major bleeding (including ICH). ROCKET-AF demonstrated non-inferiority vs. warfarin for stroke prevention with comparable major bleeding but more GI bleeding with rivaroxaban. Network meta-analyses suggest apixaban has the best bleeding profile (lowest major bleeding rates) among DOACs.

## Renal Impairment

Apixaban requires dose adjustment only for triple criteria (2 of 3: age ≥80, weight ≤60 kg, SCr ≥1.5 mg/dL). Rivaroxaban requires adjustment at CrCl <50 mL/min for AF. In severe CKD (CrCl 15–29), apixaban is more commonly used; both are generally avoided in dialysis patients.

## Key Takeaways

- Apixaban: lower GI bleeding risk, twice daily dosing, lower renal clearance (CKD advantage)
- Rivaroxaban: once daily (adherence advantage), food dependent absorption
- Both have specific reversal agent: andexanet alfa (Factor Xa inhibitor reversal)